Atıf İçin Kopyala
Bahado-Singh R. O., Graham S. F., Han B., Turkoglu O., Ziadeh J., Mandal R., ...Daha Fazla
METABOLOMICS, cilt.12, sa.6, 2016 (SCI-Expanded)
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Yayın Türü:
Makale / Tam Makale
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Cilt numarası:
12
Sayı:
6
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Basım Tarihi:
2016
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Doi Numarası:
10.1007/s11306-016-1044-3
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Dergi Adı:
METABOLOMICS
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Derginin Tarandığı İndeksler:
Science Citation Index Expanded (SCI-EXPANDED), Scopus
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Anahtar Kelimeler:
Traumatic brain injury, Metabolomics, Serum, Biomarkers, Mouse model, METABOANALYST, GLUTATHIONE, PREVALENCE, SERVER
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Dokuz Eylül Üniversitesi Adresli:
Evet
Özet
Introduction Traumatic brain injury (TBI) is physical injury to brain tissue that temporarily or permanently impairs brain function.
Objectives Evaluate the use of metabolomics for the development of biomarkers of TBI for the diagnosis and timing of injury onset.
Methods A validated model of closed injury TBI was employed using 10 TBI mice and 8 sham operated controls. Quantitative LC–MS/MS metabolomic analysis was performed on the serum.
Results Thirty-six (24.0 %) of 150 metabolites were altered with TBI. Principal component analysis (PCA) and Partial least squares discriminant analysis (PLS-DA) analyses revealed clear segregation between TBI versus control sera. The combination of methionine sulfoxide and the lipid PC aa C34:4 accurately diagnosed TBI, AUC (95 % CI) 0.85 (0.644–1.0). A combination of metabolite markers were highly accurate in distinguishing early (4 h post TBI) from late (24 h) TBI: AUC (95 % CI) 1.0 (1.0–1.0). Spermidine, which is known to have an antioxidant effect and which is known to be metabolically disrupted in TBI, was the most discriminating biomarker based on the variable importance ranking in projection (VIP) plot. Several important metabolic pathways were found to be disrupted including: pathways for arginine, proline, glutathione, cysteine, and sphingolipid metabolism.
Conclusion Using serum metabolomic analysis we were able to identify novel putative serum biomarkers of TBI. They were accurate for detecting and determining the timing of TBI. In addition, pathway analysis provided important insights into the biochemical mechanisms of brain injury. Potential clinical implications for diagnosis, timing, and monitoring brain injury are discussed.